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Publication : Regional specialization and fate specification of bone stromal cells in skeletal development.

First Author  Sivaraj KK Year  2021
Journal  Cell Rep Volume  36
Issue  2 Pages  109352
PubMed ID  34260921 Mgi Jnum  J:333199
Mgi Id  MGI:6874570 Doi  10.1016/j.celrep.2021.109352
Citation  Sivaraj KK, et al. (2021) Regional specialization and fate specification of bone stromal cells in skeletal development. Cell Rep 36(2):109352
abstractText  Bone stroma contributes to the regulation of osteogenesis and hematopoiesis but also to fracture healing and disease processes. Mesenchymal stromal cells from bone (BMSCs) represent a heterogenous mixture of different subpopulations with distinct molecular and functional properties. The lineage relationship between BMSC subsets and their regulation by intrinsic and extrinsic factors are not well understood. Here, we show with mouse genetics, ex vivo cell differentiation assays, and transcriptional profiling that BMSCs from metaphysis (mpMSCs) and diaphysis (dpMSCs) are fundamentally distinct. Fate-tracking experiments and single-cell RNA sequencing indicate that bone-forming osteoblast lineage cells and dpMSCs, including leptin receptor-positive (LepR(+)) reticular cells in bone marrow, emerge from mpMSCs in the postnatal metaphysis. Finally, we show that BMSC fate is controlled by platelet-derived growth factor receptor beta (PDGFRbeta) signaling and the transcription factor Jun-B. The sum of our findings improves our understanding of BMSC development, lineage relationships, and differentiation.
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